The prefrontal cortex (PFC) is thought to play a critical role in behavioral flexibility by monitoring action–outcome contingencies. How PFC ensembles represent shifts in behavior in response to changes in these contingencies remains unclear. We recorded single-unit activity and local field potentials in the dorsomedial PFC (dmPFC) of male rats during a set-shifting task that required them to update their behavior, among competing options, in response to changes in action–outcome contingencies. As behavior was updated, a subset of PFC ensembles encoded the current trial outcome before the outcome was presented. This novel outcome-prediction encoding was absent in a control task, in which actions were rewarded pseudorandomly, indicating that PFC neurons are not merely providing an expectancy signal. In both control and set-shifting tasks, dmPFC neurons displayed postoutcome discrimination activity, indicating that these neurons also monitor whether a behavior is successful in generating rewards. Gamma-power oscillatory activity increased before the outcome in both tasks but did not differentiate between expected outcomes, suggesting that this measure is not related to set-shifting behavior but reflects expectation of an outcome after action execution. These results demonstrate that PFC neurons support flexible rule-based action selection by predicting outcomes that follow a particular action.>SIGNIFICANCE STATEMENT Tracking action–outcome contingencies and modifying behavior when those contingencies change is critical to behavioral flexibility. We find that ensembles of dorsomedial prefrontal cortex neurons differentiate between expected outcomes when action–outcome contingencies change. This predictive mode of signaling may be used to promote a new response strategy at the service of behavioral flexibility.
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